肾小管性酸中毒骨骼并发症的临床分析

目的 总结肾小管酸中毒(Renal Tubular Acidosis,RTA)骨骼并发症的特征,探讨原发性肾小管酸中毒(Primary RTA,PRTA)与干燥综合征继发肾小管酸中毒(RTA Secondary to Sjogren's syndrome,SRTA)骨病表现的差异和特点.方法 回顾性分析本院1996年～2010年收治的原发性及干燥综合征继发性肾小管酸中毒.收集患者基本信息、临床表现,实验室检查以及同位素骨密度检查结果.比较两组患者骨病发生率以及骨骼病变的异同.结果 研究纳入PRTA共144例(男性63例、女性81例),SRTA共109例(男性10例、女性99例).PRTA患者平均年龄37.93岁,SRTA患者平均年龄42.44岁.原发组骨痛及关节痛22例(15.3％),骨量减少3例(2.1％),骨质疏松17例(11.8％),骨病变35例(24.3％).继发组骨痛及关节痛25例(22.9％),骨量减少10例(9.2％),骨质疏松9例(8.3％),骨病变患者41例(37.6％),SRTA组骨病发生率明显高于PRTA组(P＜0.05).9例PRTA患者与11例SRTA患者同位素骨密度检查发现PRTA患者腰椎T大于SRTA患者(-0.53 ±0.97 vs-1.65±1.29,P＜0.05),提示干燥组骨质疏松较原发组更为明显.结论 干燥综合征是SRTA最常见的原因,干燥综合征继发RTA患者骨病的发生率及严重程度均高于PRTA患者.     

Acidosis increases magnesiuria in children with distal renal tubular acidosis

In experimental animals, metabolic acidosis increases renal magnesium (Mg) excretion, whereas metabolic alkalosis reduces it. The objective of this study was to examine renal magnesium handling (U_Mg) in children with primary distal renal tubular acidosis (DRTA). We measured U_Mg in 11 children (3 females, 8 males, aged 6.9±4.9 years) with primary DRTA. They were studied either during spontaneous acidosis post treatment removal (3 patients) or after ammonium chloride (100 mmol/m²) induced acidosis (8 patients), and then following oral sodium bicarbonate load (4 g/1.73 m²). During acidosis (plasma pH 7.28±0.09, bicarbonate 13.2±4.3 mEq/l), U_Mg was elevated (U_Mg/Cr 0.18±0.06 mg/mg, normal values 0.1±0.06, P =0.003) although plasma Mg (P_Mg) was in the normal range (1.93±0.31 mg/dl, controls 1.77±0.19, P =NS). After acute correction of metabolic acidosis (plasma pH 7.44±0.05, bicarbonate 25.6±1.6 mEq/l, P <0.001; urine pH 7.52±0.28, bicarbonate 86.9±39.1 mEq/l), U_Mg decreased significantly ( P =0.003), returning to control values after about 2 h (U_Mg/Cr 0.09±0.06 mg/mg). Bicarbonate load resulted not only in reduction in U_Mg but also in a decrease in urinary calcium excretion (U_Ca/Cr) from 0.46±0.17 mg/mg to 0.14±0.12 mg/mg ( P <0.001). We conclude that in children with primary DRTA, urinary Mg excretion is markedly increased and that this defect, like the hypercalciuric defect, is correctable by sodium bicarbonate administration.     

远端肾小管酸中毒致泌尿系结石的诊治(附20例报告)

目的：探讨远端肾小管酸中毒(dRTA)引起泌尿系结石患者的诊断和治疗方法。方法：回顾性分析20例dRTA引起泌尿系结石患者的临床资料。结果：结石均取出或排除，术后继续使用相应药物治疗，防止结石复发。结论：dRTA引起的泌尿系结石需要相应药物治疗，同时需取出或排除结石，解除梗阻，保护肾功能。     

远端肾小管酸中毒的诊断和治疗

报告远端肾小管酸中毒１６例，其中完全型２例，不完全型１４例。完全型有高氯低钾性酸中毒，不完全型无酸中毒，但氯化铵负荷试验阳性。在口服枸橼酸钾期间，两型均观察到尿钙明显降低，尿ｐＨ和枸橼酸显著升高，完全型代谢性酸中毒得到纠正。对远端肾小管酸中毒的诊断和治疗进行了讨论。     

Diabetes and renal tubular cell apoptosis

Apoptosis contributes to the development of diabetic nephropathy, but the mechanism by which high glucose induces apoptosis is not fully understood. Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Hyperglycemia and high glucose in vitro also lead to apoptosis, a form of programmed cell death. High glucose similar to those seen with hyperglycemia in people with diabetes mellitus, lead to accelerated apoptosis, a form of programmed cell death characterized by cell shrinkage, chromatin condensation and DNA fragmentation, in variety of cell types, including renal proximal tubular epithelial cells.     

Clinical characteristics of renal tubular acidosis in adults and children

Objective To view and compare the clinical characteristics of renal tubular acidosis in adults and children. Methods Clinical data of patients with renal tubular acidosis diagnosed by Shandong Provincial Hospital affiliated to Shandong University from Jan 1991 to Sep 2017 were reviewed. The difference and consistency in clinical characteristics of renal tubular acidosis between adults and children were analyzed. Results Data from 206 adults and 60 children were analyzed. 89.81% cases in adults were secondary to other diseases, mainly primary Sjogren's syndrome. Most children patients (81.67%) were idiopathic, others largely originated from inherited metabolic diseases. The most common subtype of both was distal renal tubular acidosis. Proximal renal tubular acidosis was easier to be found in idiopathic renal tubular diseases of children. Chief complaints or starting symptoms were mainly composed of polydipsia with polyuria (41.4%) and fatigue (35.3%). Children were typical of growth retardation, rickets and digestive symptoms. The rate of missed diagnosis and misdiagnosis was 41.4 percent. Routine therapy consisted of healing metabolic acidosis and electrolyte disorders, treating underlying diseases and preventing complications. The majority of patients (95.5%) improved after treatments. Conclusions Renal tubular acidosis possesses various underlying diseases, diverse clinical manifestation and high rate of misdiagnosis. Given the high incident of secondary types, investigation of underlying disease, especially autoimmune diseases such as Sjogren's syndrome, is of great importance in adults. Most children patients suffer from primary renal tubular acidosis. Attention should be paid to them in order to reduce the rate of misdiagnosis and teratogenicity.     

A case report and review of hypokalemic paralysis secondary to renal tubular acidosis

A 5-year-old girl with distal renal tubular acidosis (RTA) and hypokalemic muscle paralysis is reported. RTA is a known cause of hypokalemia, but in spite of the presence of persistent hypokalemia muscular paralysis is uncommon, rarely described in children, and the onset of paralysis may initially be misinterpreted particularly if the patient is attended by a physician who is not a pediatric nephrologist. Therefore parents must be informed about this possibility. Still, as the clinical appearance of hypokalemic paralysis is quite similar to familial hypokalemic periodic paralysis, and because the emergent and prophylactic treatment of the two disorders are quite different, we discuss the diagnostic evaluation and the treatment for both of them.     

Efficacy and outcome of surgical intervention in patients with nephrolithiasis and chronic renal failure

Aim: To prospectively evaluate the efficacy and outcome of surgical intervention in patients with renal stones and chronic renal insufficiency.Methods: The study was carried out from January 1999 till January 2001. Only patients with chronic renal failure without medical renal disease were taken up for study. All patients were subjected to an ultrasound assessment of the kidney, ureter and bladder. In case of obstructed and infected systems a preliminary percutaneous nephrostomy was carried out. After correction of dyselectrolytemia, acid base imbalanceand dialysis (if indicated)patients were subjected to surgical intervention (open surgery or percutaneous nephrolithotomy). ESWL was offered for stones persisting after surgery. The stone burden, composition, therapeutic procedures required to render patients stone free were assessed. The outcome of stone removal on renal function was also evaluated by serial renal dynamic scans and creatinine clearance estimations.Results: Out of 90 patients operated for staghorn or calyceal calculi, complete follow up data was available in 70.Pyelo-nephrolithotomy and percutaneous nephrolithotomy was carried out in 63 and 7 patients respectively. Out of 15 patients with residual stones ESWL was successfully performed in 9 cases. Mixed, calcium oxalate monohydrate, calcium oxalate dihydrate, and struvite stones were encountered in48%, 14%, 17% and 21% respectively. The average pre operative serum creatinine was 4.76 (1.9–16) mg%.The maximum duration of follow up was 9 months. By the 9th post operative month the average fall in serum creatinine values was 1.53 mg/dl (32%)and the average functional improvement by renal dynamic scans stood at 20.665%. 41 patients were saved from further dialysis.Conclusion: Patients with mild to moderate renal failure showed maximal improvement in renal function forestalling or reducing the need for dialysis/renal replacement therapy.     

Bicarbonate therapy improves growth in children with incomplete distal renal tubular acidosis

Incomplete distal renal tubular acidosis (idRTA) has recently been associated with osteoporosis and growth retardation, attributed to the mild persistent metabolic acidosis. We hypothesized a therapeutic benefit from bicarbonate therapy on growth parameters in children with idRTA. In a study group of 40 surgically treated patients with posterior urethral valve (PUV) and normal estimated glomerular filtration rate, we evaluated the change in height standard deviation scores (SDSs) while they were on bicarbonate therapy in the presence of idRTA and complete distal renal tubular acidosis (dRTA). Age- and gender-matched healthy subjects constituted the control group (n = 55). Incomplete dRTA was evaluated by ammonium chloride acidification. The baseline height SDS of −1.94 ± 0.41 and −5.31 ± 1.95 in the groups with idRTA and complete dRTA, respectively, were significantly lower than that of the controls. After a follow-up period of 24.7 ± 8.3 months on sodium bicarbonate therapy, the idRTA patients had a 66% increase in height SDS compared with 26% and 3% increases in the patients with PUV with complete dRTA and without dRTA, respectively. At the end of follow-up, mean height SDS in the group with idRTA no longer remained significantly lower than that of the controls (P = 0.42). We concluded that bicarbonate therapy improves height SDS in idRTA. This issue needs further validation in larger studies.     

Nephrocalcinosis in glucose-galactose malabsorption, association with renal tubular acidosis

We report an association of renal tubular acidosis (RTA) in two children with glucose-galactose malabsorption (GGM), who were found to have nephrocalcinosis. Although GGM has been reported previously with nephrocalcinosis, this report is the first to show that renal tubular acidosis could explain the coexistence of nephrocalcinosis in patients with glucose galactose malabsorption.     

The syndrome of renal tubular acidosis and nerve deafness. Discordant manifestations in dizygotic twin brothers

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 Eq/min per 1.73 m²) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus bloodPCO₂ differences (U-BPCO₂) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-BPCO₂ assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.     

Distal renal tubular acidosis and ovalocytosis: a case report

A 23-year-old man presented with osteoporosis, revealed by femoral fractures, and a history of nephrolithiasis, short stature, metabolic acidosis, hypokalemia and ovalocytosis, a red blood cell abnormality common in malaria endemic regions. Biological investigations led to the diagnosis of type 1 distal renal tubular acidosis (dRTA). Ovalocytosis and dRTA may co-exist in the same patient, since both can originate in mutations of the anion-exchanger 1 (AE1) gene, which codes for band 3, the bicarbonate/chloride exchanger, present in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell.     

Hyperammonaemia in a child with distal renal tubular acidosis

A 5-month-old girl with distal renal tubular acidosis (RTA) and hyperammonaemia that had lasted for 12 days, despite metabolic acidosis correction, is presented in this report. The patient showed failure to thrive, poor feeding, hypotonia and vomiting crisis in absence of inborn errors of metabolism. Probably, hyperammonaemia was the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal RTA. Our case confirms that hyperammonaemia may be observed in distal RTA, mimicking an inborn error of metabolism, and it underlines that hyperammonaemia may persist several days after metabolic acidosis correction.     

Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium,bone and citrate metabolism

Summary Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (RTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had lower plasma standard bicarbonate after fasting (P<0.01) and lower urinary excretion of titratable acid (P<0.05) and citrate (P<0.01) compared with NUA patients and NC, and higher urinary excretion of ammonia (P<0.05) compared with NC (P<0.05). Hypercalciuria was found in 6 of 10 patients with iRTA compared with 3 of 10 with NUA, and O of 10 NC. The citrate/calcium ratio in urine was significantly reduced in iRTA compared with the value in NUA (P<0.01), and in NUA compared with NC (P<0.05). Biochemical markers of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were significantly increased in iRTA compared with NUA and NC (P<0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism-the same metabolic abnormalities which characterize classic type 1 RTA. Mild non-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA     

肾小管酸中毒患者的骨矿物含量变化

使用ＳＤ－１００单光子吸收骨密度仪对２４例肾小管性酸中毒患者进行了左侧尺桡骨中前１／３处骨矿含量的测定并与正常人骨密度进行了比较。结果显示９５．８３％的患者有骨矿物质含量的下降，而Ｘ线的异常改变仅占３３．３３％，提示骨矿物质含量的测定对于提早发现肾小管性酸中毒的骨病优于Ｘ线的检查。     

Metabolic acidosis in dextran-induced anaphylactic reactions

Results of arterial blood gas and acid-base balance analyses were analyzed in 50 patients suffering from dextran-induced anaphylactic reactions. Metabolic acidosis was always present in severe cases, leading to cardiac arrest, and also frequently found in those with less severe reactions with only slightly impaired circulation. Bronchospastic respiratory signs were frequently encountered but acidosis was noted to develop even without these symptoms. The severity of the acidosis was generally underestimated during treatment. Arterial PO2 and PCO2 were not significantly affected during these reactions.     

Prevalence and densitometric characteristics of incomplete distal renal tubular acidosis in men with recurrent calcium nephrolithiasis

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO₄/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm²): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm²): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.     

Kidney stone inhibitors in patients with renal stones and endemic renal tubular acidosis in northeast Thailand

Distal renal tubular acidosis (dRTA) is generally associated with hypercalciuria, hypocitraturia, and nephrolithiasis. Our intention was to study glycosaminoglycans (GAGS) and nephrocalcin (NC), two well-known crystal growth inhibitors, in a population with endemic dRTA and nephrolithiasis in northeast (NE) Thailand. We studied 13 patients, six with dRTA and seven with nephrolithiasis with normal or undefined acidification function. Six healthy adults living in the same area as the patients and another six from the Bangkok (BKK) area were used as controls. We measured urinary pH, ammonia, calcium, citrate, magnesium, oxalate, potassium, sodium and uric acid. GAGS were determined by an Alcian blue precipitation method and were qualitated by agarose gel electrophoresis after being isolated using 5% cetyltrimethylammonium bromide at pH 6.0. NC isoforms were isolated as previously described by Nakagawa et al. Citrate was higher in BKK controls (p<0.04). There was a striking difference among GAGS from BKK when compared with other groups (103.85±10.70 vs. 23.52±8.11 for dRTA, 22.36±14.98 for kidney stone patients and 14.73±2.87 mg/ml in controls from the NE region, (p<0.0001). dRTA and stone-forming patients excrete proportionally more (C+D) than (A+B) NC isoforms (p<0.05). Also, their NC showed a 100-fold weaker binding capacity of calcium oxalate monohydrate crystals. The ratio of chondroitin sulfate/heparin sulfate in GAGS was approximately 9/1. In addition to the traditional risk factors for nephrolithiasis in dRTA, GAGS and NC might play an important role in the pathogenesis of stone formation in this population.